Inclusion Criteria:

- Histologically or cytologically confirmed colorectal cancer, excluding primary tumors
of appendiceal origin (participants are eligible to enroll irrespective of KRAS
mutation status)

- Confirmed metastatic colorectal cancer (Stage IV)

- The participant has received first-line combination therapy of bevacizumab,
oxaliplatin, and a fluoropyrimidine for metastatic disease and a) Experienced
radiographic disease progression during first-line therapy, or b) Experienced
radiographic disease progression ≤ 6 months after the last dose of first-line
therapy, or c) Discontinued part or all of first-line therapy due to toxicity and
experienced radiographic disease progression ≤ 6 months after the last dose of
first-line therapy; Note that a participant must have received a minimum of 2 doses
of bevacizumab as part of a first-line regimen containing chemotherapy; in addition,
a participant must have received at least 1 cycle of first-line therapy that included
bevacizumab, oxaliplatin and a fluoropyrimidine in the same cycle; Note that a
participant must not have received more than 2 different fluoropyrimidines as part of
a first-line regimen; disease progression is not an acceptable reason for
discontinuing one fluoropyrimidine and starting a second fluoropyrimidine

- Receipt of no more than 2 prior systemic chemotherapy regimens in any setting (only 1
prior regimen for metastatic disease is permitted); For participants with rectal
cancer, sequential neoadjuvant and adjuvant therapy will count as a single systemic
regimen; Note that rechallenge with oxaliplatin is permitted and will be considered
part of the first-line regimen for metastatic disease, both initial oxaliplatin
treatment and subsequent rechallenge are considered as 1 regimen

- Measurable or nonmeasurable disease based on the Response Evaluation Criteria in
Solid Tumors, Version 1.1 (RECIST v. 1.1)

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

- Adequate hematologic, renal and hepatic function

- Adequate coagulation function (International Normalized Ratio [INR] ≤1.5 and Partial
Thromboplastin Time [PTT] or activated PTT [aPTT] ≤1.5 X upper limit of normal
[ULN]). Participants on full-dose anticoagulation must be on a stable dose of
anticoagulant therapy and if on oral anticoagulation, must have an INR ≤3 and have no
clinically significant active bleeding or pathological condition that carries a hish
risk of bleeding

- Consent to provide a historical colorectal cancer tissue sample for assessment of
biomarkers and the tumor tissue sample is available

- Ability to provide signed informed consent

Exclusion Criteria:

- Receipt of bevacizumab ≤ 28 days prior to randomization

- Receipt of any investigational therapy for non-oncology clinical indication ≤ 28 days
prior to randomization

- Receipt of any previous systemic therapy, other than a combination of bevacizumab,
oxaliplatin, and a fluoropyrimidine, for first-line treatment of metastatic
colorectal cancer

- Known leptomeningeal disease or brain metastases or uncontrolled spinal cord
compression (currently or in the past)

- Experience of any arterial thrombotic or arterial thromboembolic events, including,
but not limited to myocardial infarction, transient ischemic attack, or
cerebrovascular accident, ≤ 12 months prior to randomization

- Pregnant (confirmed by serum beta human chorionic gonadotropin [ß HCG] test ≤ 7 days
prior to randomization) or lactating

- History of inflammatory bowel disease or Crohn's disease requiring medical
intervention (immunomodulatory or immunosuppressive medications or surgery) ≤ 12
months prior to randomization

- Acute or subacute bowel obstruction or history of chronic diarrhea which is
considered clinically significant in the opinion of the investigator

- Grade 3 or higher bleeding event ≤ 3 months prior to randomization

- Experience of any of the following during first-line therapy with a
bevacizumab-containing regimen: an arterial thrombotic/thromboembolic event, Grade 4
hypertension, Grade 3 proteinuria, a Grade 3-4 bleeding event, or bowel perforation

- Known history or clinical evidence of Gilbert's Syndrome, or is known to have any of
the following genotypes: UGT1A1*6/*6, UGT1A1*28/*28, or UGT1A1*6/*28

- Known allergy to any of the study treatment components, including any components used
in the preparation of ramucirumab, or other contraindication to receive the study
treatments

- Cirrhosis at a level of Child-Pugh B (or worse) or cirrhosis (any degree) and a
history of hepatic encephalopathy or clinical meaningful ascites resulting from
cirrhosis; Clinically meaningful ascites is defined as ascites resulting from
cirrhosis and requiring ongoing treatment with diuretics and/or paracentesis