Inclusion Criteria

• Diagnosis of metastatic adenocarcinoma of the colon or rectum that cannot, in the opinion of the investigator, be cured by surgical resection at the time of randomization
• Wild-type KRAS expressing mCRC from the primary tumor or metastasis.
• Failure of prior first-line oxaliplatin-based chemotherapy with bevacizumab (at least four therapeutic doses of oxaliplatin-based chemotherapy and bevacizumab) for mCRC.
• At least one uni-dimensionally measurable lesion per modified RECIST criteria.
• Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Man or woman 18 years of age or older
• Hematology, chemistry, coagution, metabolic functions within normal or protocol-defined limits

Exclusion Criteria

• Previous irinotecan, anti-EGFr therapy (eg, cetuximab, panitumumab, erlotinib, gefitinib, lapatinib) or vaccine for the treatment of mCRC
• Radiotherapy ≤ 14 days before randomization
• Evidence of central nervous system (CNS) metastases
• Unresolved toxicities from prior anti-cancer therapy that, in the opinion of the investigator, precludes subject from participation
• History of other invasive primary cancer, except:
• Curatively resected or treated non-melanomatous skin cancer
• Curatively treated cervical carcinoma in situ
• Other primary solid tumor treated curatively and no treatment administered ≤ 2 years before randomization and, in the investigator's opinion, it is unlikely that there will be a recurrence ≤ 2 years post randomization

Medications

• C hronic daily treatment (as determined by the investigator) with aspirin (> 325 mg/day) or non steroidal anti inflammatory agents known to inhibit platelet function
• Infection requiring a course of systemic anti-infectives that was completed ≤ 14 days before randomization (exception can be made at the judgment of the investigator for oral treatment of an uncomplicated urinary tract infection [UTI])
• Subjects concurrently receiving any investigational agent or therapy ≤ 30 days before randomization

General:

• Significant cardiovascular risk as defined by the protocol
• History of peripheral arterial ischemia ≤ 24 weeks before randomization (subjects with brief, reversible, exercise-induced claudication are eligible)
• History of visceral arterial ischemia ≤ 24 weeks before randomization
• Significant bleeding risk:
• Major surgical procedure, open biopsy, or significant traumatic injury ≤ 28 days before randomization
• Anticipation of need for major surgical procedures during the course of the study
• C ore biopsy or other minor procedure, excluding placement of a vascular access device ≤ 7 days before randomization
• A ny significant bleeding that is not related to the primary colon tumor ≤ 24 weeks before randomization
• P re-existing bleeding diathesis or coagulopathy with the exception of well-controlled chronic anticoagulation therapy
• Serious or non-healing wounds, skin ulcers, or unhealed bone fractures
• Gastroduodenal ulcer(s) determined by endoscopy to be active or uncontrolled gastrointestinal ulcer ≤ 28 days before randomization
• History of interstitial lung disease (eg, pneumonitis or pulmonary fibrosis) or evidence of interstitial lung disease on baseline chest x-ray (CXR) or computed tomography (CT) scan
• Clinically significant ascites
• Subjects known to be human immunodeficiency virus (HIV) positive or known to have chronic or active hepatitis B or C infection
• Men and women of childbearing potential (women who are post-menopausal < 52 weeks, not surgically sterilized, or not abstinent) who do not consent to use adequate contraception (according to institutional standard of care) during the course of the study and after the last date of receiving second-line treatment (24 weeks for women, 4 weeks for men)
• Women who test positive for serum or urine pregnancy test ≤ 72 hours before randomization or are breast-feeding
• Subjects allergic to any component that is part of the treatment regimen