Fourteen patients with 5-fluorouracil (5-FU) refractory, progressive colorectal cancer metastatic to liver and/or lung were treated with continuous oral trofosfamide, an alkylating agent structurally related to cyclophosphamide and ifosfamide. Trofosfamide was given daily at 200 mg/day. No objective partial or complete responses were seen in 14 evaluable patients. There were four patients with stable disease or minor responses; the median duration of stable disease during trofosfamide treatment was 14 weeks, with of range of 12-36 weeks. Mild to moderate side effects were reported in seven patients including grade 1-2 nausea in four patients, grade 1 leukopenia in two patients and grade 1 anemia in one patient. Trofosfamide in this dose and schedule shows minor activity in 5-FU refractory colorectal cancer. Because of very little side effects, dose escalations appear to be possible.