The combination of 5-fluorouracil (5-FU) and folinic acid (FA) has demonstrated activity in colorectal cancer (CC). Cisplatin is reported to have synergistic activity with 5-FU. We examined the combination FA + 5-FU + cisplatin in patients who had previously received chemotherapy with FA + 5-FU and relapsed. Two months after the last dose of FA + 5-FU and documentation of relapse, patients continued with the regimen consisting of cisplatin 20 mg/m2 in 15 min i.v. infusion followed by FA 500 mg/m2 in 1 h i.v. infusion, in the middle of which 5-FU 500 mg/m2 i.v. bolus was administered, with adequate post-hydration. This was repeated weekly for 4 weeks followed by a 2 week rest, for a maximum of six cycles. A total of 30 patients with CC that had relapsed to the combination of FA + 5-FU were treated; 23 had previous surgery and none had radiotherapy. Local recurrence was found in eight patients, metastases in the liver in 21, in lymph nodes in six, lung six and peritoneal metastases in seven. Seven patients responded partially. Toxicity requiring dose reduction or discontinuation of treatment included neutropenia 42% (grade 3:7%), mucositis 28% (grade 1:2), diarrhea 63% (Grade 3:10%), nausea-vomiting 55% (Grade 3:10%), increased creatinine value in three patients and peripheral neuropathy in two patients. We conclude that evaluation of this regimen shows substantial toxicity, with satisfactory response as a second line chemotherapy in these heavily pretreated patients.