Inclusion Criteria:

Disease-related

- Histologically or cytologically-confirmed adenocarcinoma of the colon or rectum

- Locally-advanced or metastatic disease by radiographic evaluation

- Measurable disease

- Subject has not previously received chemotherapy for locally-advanced or metastatic
colorectal cancer. Subject may have received adjuvant therapy for primary colorectal
cancer provided that at least 6 months have elapsed from the time the adjuvant
therapy was concluded and recurrent/metastatic disease was documented.

- Performance status 0-2

Demographic

- Age of 18 years or over

Laboratory

Adequate organ and marrow function as defined below:

- Absolute neutrophil count at least 1.5 x 109/L

- Platelet count at least 100 x 109/L

- Bilirubin ≤ 1.5 times upper limit of normal

- Aspartate aminotransferase and alanine aminotransferase ≤ 2.5 x upper limit of normal
or Aspartate aminotransferase and alanine aminotransferase ≤ 5.0 x upper limit of
normal if attributable to liver metastasis

- An in-range INR (in-range is usually defined as between 2 and 3) for subjects on a
stable dose of oral anticoagulant or stable dose of low molecular weight heparin

- Subject has no active bleeding or pathological condition that carries high risk of
bleeding (eg, tumor involving major vessels or known varices). If a suspicion of
bleeding diathesis exists, a bleeding time should be performed

- Creatinine ≤ 1.5 times upper limit of normal

General

- Written informed consent obtained

- Afebrile on day 1 of cycle 1

- Must be able and willing to comply with study and/or follow-up procedures

Exclusion Criteria:

Disease-Related

- Known brain metastases

- History of another primary malignancy less than/equal to 5 years prior to
randomization, with the exception of non-melanoma skin cancer, carcinoma in situ of
uterine cervix, and prostatic intraepithelial neoplasia without evidence of prostate
cancer

- Prior major surgical procedure less than 28 days prior to day 1 of cycle 1
chemotherapy dosing; anticipated need for major surgical procedure during the 4 cycle
treatment period of the study

- Fine needle aspirations or core biopsies within 7 days prior to day 1 of cycle 1
chemotherapy dosing

- Serious nonhealing wound, ulcer, or bone fracture, or history of abdominal fistula,
gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to day
1 of cycle 1

- Uncontrolled high blood pressure, history of labile hypertension, uncontrolled
congestive heart failure, unstable angina within the past 3 months, myocardial
infarction or history of stroke within the past 12 months, unstable symptomatic
arrhythmia requiring medication, or clinically significant peripheral vascular
disease

- History of clinically significant bleeding within 6 months prior to randomization

- History of arterial or venous thromboembolism within 6 months prior to randomization

- History of other disease including uncontrolled diabetes, serious active or
uncontrolled infection, metabolic dysfunction; physical examination finding, or
clinical laboratory finding giving reasonable suspicion of a disease or condition
that contraindicates the use of the prescribed therapy or that might affect the
interpretation of the results of the study or render the subject at high risk from
treatment complications

Laboratory

- Proteinuria > 1+, or total quantitative protein > 500 mg protein/day as determined by
24-hr urine collection

Medications

- Prior radiotherapy unless treatment was limited to the target lesion and only 1
measurable lesion was treated. Progression of the irradiated lesion must be
demonstrated. Subjects may not have received prior radiotherapy to greater than 25%
of bone marrow. Radiation must have concluded ≥ 4 weeks prior to enrollment. Prior
radio-sensitizing chemoradiation will be allowed as long as it was concluded ≥ 4
weeks prior to enrollment.

- Radiotherapy to non-target lesions for pain control will be allowed

- Prior bevacizumab use or other agents targeting VEGF

- Concurrent use of other biological agents

- Use of systemic anti-infectives for active infection, during the 3 calendar days
before starting study chemotherapy and bevacizumab or planned during the study
treatment period

General

- Current, recent (within 4 weeks of the first infusion of this study), or planned
participation (during the study treatment period) in an experimental therapeutics
study other than this protocol

- Female subjects who are pregnant or lactating or men and women of reproductive
potential not willing to employ an effective method of birth control during treatment
and for 20 weeks for women, and 30 weeks for men after discontinuing study treatment

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to bevacizumab, irinotecan, 5-FU, oxaliplatin, or leucovorin, including
known sensitivity to E.Coli derived products (eg, Filgrastim, HUMULIN insulin,
L-asparaginase)

- Known dihydropyrimidine dehydrogenase deficiency