Inclusion Criteria:

- Signed Informed Consent Form

- Age >= 18 years

- Histologically confirmed CRC with evidence of metastases and measurable tumor
lesion(s)

- Progression of disease following, or intolerance to, treatment with
5-fluorouracil-based therapy

- Progression of disease during or within =< 6 months following the last dose of a
prior first-line treatment with a fluoropyrimidine and oxaliplatin-based chemotherapy
plus bevacizumab for metastatic disease

- Use of an effective means of contraception for women of childbearing potential and
men with partners of childbearing potential (use per institutional standard)

- Life expectancy of > 3 months

- Willingness and capability to be accessible for study follow-up

Exclusion Criteria:

- Prior radiotherapy to a measurable, metastatic lesion(s) to be used to measure
response

- Radiation therapy to a peripheral lesion within 14 days prior to Day 1; Radiation
therapy to a thoracic, abdominal or pelvic field within 28 days prior to Day 1

- Chemotherapy, hormonal therapy, or immunology within 4 weeks prior to Day 1

- Previous exposure to DR4-targeted therapy or DR5-targeted therapy

- Evidence of clinically detectable ascites on Day

- Other invasive malignancies within 5 years prior to Day 1 (other than basal cell
carcinoma of the skin or in situ carcinoma of the cervix)

- History or evidence upon physical examination of CNS disease

- Active infection requiring parenteral antibiotics on Day 1

- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
prior to Day 1 or anticipation of need for major surgical procedure during the course
of the study and fine needle aspirations within 7 days prior to Day 1

- Pregnancy or lactation

- Serious nonhealing wound, ulcer, or bone fracture

- Current or recent participation in another experimental drug study

- Clinically significant cardiovascular disease

- History of other disease, metabolic dysfunction, physical examination finding, or
clinical laboratory finding giving reasonable suspicion of a disease or condition
that contraindicates use of an investigational drug or that might affect
interpretation of the results of the study or render the subject at high risk from
treatment complications

- Cohort 5 only: Subjects who have a Kras mutation will be excluded from enrollment

- The following exclusion criteria apply only to subjects who have received prior
bevacizumab and are enrolled in Cohort 6: four or more prior doses of bevacizumab
therapy, inadequately controlled hypertension, history of hypertensive crisis or
hypertensive encephalopathy, history of arterial thromboembolic event 6 months prior
to Day 1, proteinuria, history of abdominal fistula or gastrointestinal perforation
within 6 months prior to Day 1