Several studies suggest that protracted continuous Infusion constitutes an important way to optimize the dose and the efficacy of 5-fluorouracil (5-FU) in metastatic cancer. Eighty-three women aged 27–76 (median age 55) with metastatic breast cancer were treated every 4 weeks with a continuous ambulatory venous infusion of 5-FU 350 mg/m2/day and oral cyclophosphamide 100 mg/m2/day over 15 days. The continuous therapy was associated with a weekly administration of vincristine (0.8 mg/m2) and doxorubicin (15 mg/m2) on day 1, day 8, and day 15. Cycles were repeated every 28 days. Thirty-four patients were treated in first-line metastatic chemotherapy and 49 in second-line. Toxicities included: mucositis (grade≤2) 23%, diarrhea (grade≤2) 7%, a hand-foot syndrome (grade≤2) 9%, alopecia (grade 3) 21%, neurological (grade≤2) 4%, grade 3 and 4 leukopenia 29%, and grade 3 and 4 thrombopenia 8%. Heart toxicity was only 3%. Catheter infection was observed in 1 case and 7 patients experienced thrombosis. The overall objective response rate (OR) was 48% and the complete response rate was 23%. The median duration of response was 10 months. The median survival was 16 months. Activity was better in naive than pretreated women (respectively, 55% and 42% of OR, p = 0.21). Analysis of responses according to the metastatic sites shows the pronounced efficacy on soft tissus diseases (skin recurrences 42%, lymph nodes 52%), and also in visceral metastases (hepatic 36%, lung 34%).