Previous results suggest that GEM affects 5-fluorouracil (5-FU) metabolism and pharmacokinetics in cancer patients, while combined with oxaliplatin, levo-folinic acid, and 5-FU (GOLF regimen), at doses achievable in cancer patients, determines high cytotoxic and proapoptotic antitumour activity in colon cancer cells in vitro. On these bases we designed a phase I-II clinical trial testing the GOLF regimen in patients with metastatic colorectal carcinoma, who had received at least a prior line of chemotherapy. In total, 29 patients (20 males and nine females) enrolled in the study received every 2 weeks, gemcitabine (patients #1-3 received 600 mg m(-2); patients # 4-6 received 850 mg m(-2); while patients # 7-29 received 1000 mg m(-2)) on the day 1, levo-folinic acid (100 mg m(-2)) on the days 1 and 2; 5-fluorouracil (400 mg m(-2)) in bolus injection, followed by a 22-h continuous infusion (800 mg m(-2)) on the days 1 and 2, and oxaliplatin (85 mg m(-2)), 6 h after the 5-FU bolus on day 2. The most frequent side effect was grade I-II haematological toxicity. In total, 28 patients were evaluable for response: three achieved a complete response, nine a partial response, 10 had a stable disease, and six progressed. The average time to progression and overall survival of the patients was, respectively, 7.26 and 22 months. Our GOLF combination is well tolerated and seems promising for the treatment of advanced colorectal cancer.