A Phase 2, Randomized, Double Blind, Placebo Controlled Study of AMG 386 in Combination With FOLFIRI in Subjects With Previously Treated Metastatic Colorectal Carcinoma

Inclusion Criteria:

* Histologically confirmed adenocarcinoma of the colon or rectum in patients who are presenting with metastatic disease
* One and only one prior chemotherapy regimen for metastatic disease consisting of the combination of a fluoropyrimidine-based chemotherapy and an oxaliplatin-based chemotherapy. Prior adjuvant chemotherapy used prior to the onset of metastatic disease is permitted
* At least one uni dimensionally measurable lesion per modified RECIST criteria. All sites of disease must be evaluated \<= 28 days before randomization
* Radiographically documented disease progression per modified RECIST criteria either while receiving or \<= 6 months after the last dose of prior chemotherapy regimen for metastatic disease
* ECOG performance status of 0 or 1
* Man or woman \>= 18 years of age
* Adequate end organ assessments by laboratory studies (hematological and chemistries)
* Life expectancy \>= 3 months

Exclusion Criteria:

* Exclude subjects with a history of prior malignancy, except:

  * Malignancy treated with curative intent and with no known active disease present for \>= 3 years before enrollment and felt to be at low risk for recurrence by treating physician
  * Adequately treated non-melanomatous skin cancer or lentigo maligna without evidence of disease
  * Adequately treated cervical carcinoma in situ without evidence of disease
  * Prostatic intraepithelial neoplasia without evidence of prostate cancer
* Prior irinotecan therapy
* Systemic chemotherapy, hormonal therapy, or immunotherapy \<= 21 days prior to randomization
* Experimental or approved proteins/antibodies (eg, bevacizumab) \<= 30 days prior to randomization
* Clinically significant cardiac disease within 12 months prior to randomization, including myocardial infarction, unstable angina, grade 2 or greater peripheral vascular disease, cerebrovascular accident, transient ischemic attack, congestive heart failure, or arrhythmias not controlled by outpatient medication, percutaneous transluminal coronary angioplasty/stent
* Known allergy or hypersensitivity to irinotecan, 5 FU (known dihydropyrimidine dehydrogenase deficiency) or leucovorin
* Active inflammatory bowel disease or other bowel disease causing chronic diarrhea (defined as \>= CTC grade 2 \[CTCAE version 3.0\])