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.