A Study of Irinotecan and Cetuximab With or Without IMC-A12 for Treatment of Participants With Colon or Rectum Cancer Who Got Worse After Their First Treatment With Oxaliplatin and Bevacizumab

Inclusion Criteria:

* Must consent to be in the study and must have signed and dated Institutional Review Board (IRB)-approved consent forms conforming to federal and institutional guidelines for the pre-entry tumor sample submission for central K-RAS testing and for the study treatment
* Must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
* Must have metastatic CRC
* The CRC tumor or metastatic tumor must be v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog gene (K-RAS) wild-type as determined by central testing
* Must be documented disease progression during first-line therapy containing both oxaliplatin and bevacizumab
* Most recent treatment regimen must have ended ≥21 days prior to randomization, and clinically significant side effects associated with previous therapy must have resolved to ≤Grade 1 with the exception of neuropathy which must have resolved to ≤Grade 2
* Imaging of the chest, abdomen and pelvis with computed tomography (CT) scan or magnetic resonance imaging (MRI) must be performed within 3 weeks prior to randomization
* Must have measurable disease, defined as at least 1 lesion outside a previous radiation therapy (RT) field that can be accurately measured in at least 1 dimension as ≥20 millimeters (mm) with conventional techniques or as ≥10mm with 5mm cuts using a spiral CT scan
* Evidence of adequate bone marrow function: absolute neutrophil (ANC) ≥1200 cubed millimeters (mm³), hemoglobin ≥9 grams per deciliter (g/dL), platelets ≥100,000 mm³
* Evidence of adequate hepatic function. If no liver metastases: aspartate aminotransferase (AST) ≤2.5 times (x) upper limit of normal (ULN), total bilirubin ≤1.5 x ULN for the lab. In the presence of liver metastases: AST ≤5.0 x ULN, total bilirubin ≤1.5 x ULN for the lab
* Serum creatinine must be ≤1.5 x ULN for the lab
* Must have a fasting blood glucose \<126 milligrams/deciliter (mg/dL). Fasting is defined as no caloric intake for at least 8 hours

Exclusion Criteria:

* Life expectancy less than 12 weeks
* Diagnosis of anal or small bowel carcinoma
* Tumor that is considered by the surgeon to be amenable to complete resection
* Previous RT to \>25% of bone marrow
* RT to sites of measurable disease chosen as target lesions
* Radiological evidence and/or clinical signs or symptoms of central nervous system (CNS) metastases
* Any of the following conditions and events: uncontrolled hypertension, defined as systolic blood pressure (BP) \>150 millimeters of mercury (mmHg) or diastolic BP \>100 mmHg with or without antihypertensive medication (participants with hypertension that is well-controlled on medication are eligible); unstable angina within 6 months before randomization; New York Heart Association (NYHA) Class III or IV cardiac disease; myocardial infarction (MI) within 6 months before randomization; symptomatic arrhythmia; CNS cerebrovascular ischemia \[transient ischemic attack (TIA) or stroke\] within 6 months before randomization
* Other malignancies unless the participant is considered to be disease-free and has completed therapy for the malignancy ≥12 months prior to randomization. Participants with the following cancers are eligible if diagnosed and treated within the past 12 months: carcinoma in situ of the cervix, colon carcinoma in situ, melanoma in situ, and basal cell and squamous cell carcinoma of the skin
* Serious or non-healing wound, skin ulcers, or bone fracture
* Any significant bleeding unless the source of bleeding has been resected
* History of bleeding diathesis or coagulopathy (participants on stable anticoagulant therapy are eligible)
* Any evidence of active infection
* Active inflammatory bowel disease
* Grade 3 or 4 diabetes mellitus as defined by National Cancer Institute's (NCI's) Common Terminology Criteria for Adverse Events (CTCAE) v 3.0 pancreatic endocrine: glucose intolerance (participants with diabetes controlled with diet and/or oral medications are eligible)
* Symptomatic interstitial pneumonitis or definitive evidence of interstitial pneumonitis described on CT scan or chest x-ray in asymptomatic participants
* Any other serious concomitant medical condition that, in the opinion of the investigator, would compromise the safety of the participant or compromise the participant's ability to participate in the study
* Previous hypersensitivity reaction to monoclonal antibodies
* Previous treatment with irinotecan, cetuximab, or any agent specifically targeting insulin-like growth factor (IGF) receptors
* Treatment with an investigational drug within 30 days prior to randomization
* Pregnancy or lactation at the time of participant entry
* Psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude the participant from meeting the study requirements