Forty three patients with metastatic colorectal cancer (MCC) received a daily administration of 5-fluorouracil (600 mg/m2/d at the first course, 700 mg/m2/d at the second and 800 mg/m2/d at the third course), and l-folinic acid (150 mg/m2/d) or dl-folinic acid (300 mg/m2/d) both chronomodulated from 22:00 to 10.00 am with peak delivery rate at 4.00 for 5 days every 21 days. Only severe mucositis and diarrhea occurred in 19 courses (5.7% Gr 3; 0.6% Gr 4) in 14 patients. Objective response (OR) was evaluated in 40 patients because of one toxicity and two early progressions. No OR was observed in the 15 previously-treated patients versus 28.5% (8/28) partial responses in chemotherapy naïve patients; overall the median survival was 13 months. These results without toxicity and with low OR rate indicate the necessing of a more intensive treatment and confirm the place of oxaliplatin in the chemotherapy of MCC.