Inclusion Criteria: - Able to comprehend and sign an Institutional Review Board (IRB)-approved informed consent form - Pathologic diagnosis of colorectal cancer - Metastatic colorectal adenocarcinoma - If history of adjuvant chemotherapy for colorectal cancer, must have been free of disease for greater than or equal to 1 year after completion of adjuvant chemotherapy - Unidimensionally measurable disease - Paraffin-embedded tumor tissue available for immunohistochemistry studies of epidermal growth factor receptor (EGFr) expression (archived tissue is acceptable) - Tumor over-expressing EGFr by immunohistochemistry (staining must be the sum of 1+, 2+ and 3+ in greater than or equal to 10% of evaluated tumor cells; staining and evaluation to be conducted at a central laboratory) - ECOG score of 0 or 1 - Adequate hematologic, renal, and hepatic function Exclusion Criteria: - Female subject (of childbearing potential, post-menopausal for less than 6 months, not surgically sterilized, or not abstinent) not consenting to use adequate contraceptive precautions during the course of the study and for 6 months after the last ABX-EGF infusion - Female subject who is breast-feeding or pregnant - Any kind of disorder that compromises the ability of the subject to give written informed consent and/or comply with the study procedures - History of any chronic medical or psychiatric condition or laboratory abnormality that, in the opinion of the investigator, may increase the risks associated with study participation or study drug administration or may interfere with subject compliance or the interpretation of study results - Untreated brain metastases - Therapy for colorectal cancer other than surgery and 5-FU-based adjuvant therapy - Prior treatment for metastatic colorectal cancer - Prior irinotecan - Prior or concurrent radiation therapy for colorectal cancer, including prior adjuvant radiation therapy to the pelvis - Known allergy to irinotecan, 5-fluorouracil, or leucovorin - Known Gilbert's disease - Known dihydropyrimidine dehydrogenase (DPD) deficiency - Prior EGFr-targeting agents - Use of investigational therapy used with adjuvant intent within 30 days before the first ABX-EGF infusion - If prior history of cancer other than colorectal carcinoma, basal cell carcinoma, or cervical carcinoma in situ, no treatment or active disease within 5 years - Active inflammatory bowel disease or other bowel disease (other than colorectal carcinoma) causing chronic diarrhea (defined as greater than 4 stools per day) - Partial or complete bowel obstruction, known chronic malabsorption, total colectomy, or other major abdominal surgery that might result in substantial alteration in transit to absorption of oral medication - Ascites or pleural effusion requiring therapeutic paracentesis or thoracentesis; subject with small, stable, asymptomatic pleural effusions or ascites may be enrolled; subject who has been rendered asymptomatic by successful sclerosis of an effusion may be enrolled. - Active interstitial pneumonia or interstitial fibrosis - Left ventricular ejection fraction (LVEF) less than 45%, as measured by multiple-gated acquisition (MUGA) scan - Myocardial infarction within 1 year before the first ABX-EGF infusion - Any of the following within 6 months before the first study drug dose:

• Unstable angina;
• Symptomatic congestive heart failure;
• Serious uncontrolled cardiac arrhythmia;
• Cerebrovascular accident or transient ischemic attack;
• Pulmonary embolism;
• Deep vein thrombosis;
• Other significant thromboembolic event. - Subject known to be HIV positive - History of any chronic medical or psychiatric condition or laboratory abnormality that, in the opinion of the Investigator, may increase the risks associated with study participation or study drug administration or may interfere with patient compliance or the interpretation of study results - Subject unwilling or unable to comply with study requirements - Known allergy to the ingredients of the study drug or to Staphylococcus protein A