Inclusion Criteria:

• Patients with histologically proven metastatic adenocarcinoma of the colon or rectum
• Previous chemotherapy for metastatic disease not allowed. Patients who received prior adjuvant 5-FU-based chemotherapy are eligible if they have remained free of disease for at least 6 months after the completion of adjuvant therapy
• Patients with operable metastatic disease are excluded from the study
• Age 18-70 years
• Performance status (ECOG) 0-1
• At least one bidimensionally measurable lesion of >= 2cm
• Life expectancy of at least 6 months
• Adequate hematologic parameters (absolute neutrophil count >= 1.5x109/L and platelets >=100x109/L)
• Creatinine and total bilirubin < 1.25 times the upper limit of normal
• Aspartate and alanine aminotransferase < 3.0 times the upper limit of normal (<5 times in case of liver mets)

Exclusion Criteria:

• Absence of active infection or malnutrition (loss of more than 20% of the body weight)
• No history of a second primary tumor other than non-melanoma skin cancer or in situ cervical carcinoma. curatively treated
• Patients treated with palliative radiotherapy had to have measurable metastatic disease outside the irradiation fields.
• Patients with severe cardiac dysfunction, liver metastases involving more than 50% of the liver parenchyma, chronic diarrhea, or prior irradiation affecting more than 30% of the active bone marrow are excluded.
• All patients will have to sign written informed consent in order to participate in the study