27 patients with advanced colorectal cancer were treated in a phase-II trial with high dose sequential methotrexate (MTX), 5-fluorouracil (5-FU), and folinic acid (FA). Following a 4 h infusion of 800 mg/m2 MTX and a 4 h interval, 1,500 mg/m2 5-FU and 200 mg/m2 FA were given as a 24 h infusion. Out of 23 evaluable patients we observed one partial remission and 9 disease stabilizations. Median survival time of all patients was 10.4 months. Overall toxicity was low. In comparison to a previous trial we did not observe better treatment results by adding high dose FA to a sequential MTX/5-FU schedule.