Trial of FOLF(HA)Iri Versus FOLFIRI in mCRC

Inclusion Criteria: * Metastatic colorectal cancer with disease progression after first or second line chemotherapy * Irinotecan naïve. * ECOG performance status of 0 or 1. * Measurable disease, i.e. at least one measurable metastatic lesion (spiral CT or MRI). * Histological proof of colorectal cancer. * 18 years of age and older. * Adequately recovered from and at least 4 weeks after recent surgery or chemotherapy. * Women of child-bearing potential (WOCBP) and male partners of WOCBP must agree to use adequate contraception. * Patient consent obtained and signed according to local and/or national ethics. * CT or MRI scan of chest/abdomen/pelvis within 21 days prior to randomization. * Hematology done within 14 days prior to randomization. * Chemistry done within 14 days prior to randomization. Exclusion Criteria: * History of other malignancies, except adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumors curatively treated with no evidence of disease for \> 5 years. * Locally advanced or recurrent disease only. * Unsuitability for irinotecan including known Gilbert's syndrome, active inflammatory bowel disease or chronic diarrhea greater than or equal to grade 2. * Abdominal or pelvic radiation therapy within the last 12 months. * Women who are pregnant or breastfeeding. * Any condition (e.g., psychological, geographical) that would render the protocol treatment dangerous. * Significant cardiac disease. * Untreated or symptomatic brain or central nervous system (CNS). * Presence of pleural effusion or ascites requiring therapeutic thoracocentesis or paracentesis. * Current partial or complete bowel obstruction. * Concomitant active infection. * Enrolled in any other investigational trial, unless treatment in that trial has been discontinued at least 30 days prior to signing the Informed Consent for the ACO-002 study.