The external validity of trial results is a matter of debate, and no strong evidence is available to support whether a trial may have a positive or a negative effect on the outcome of patients. Methods. We compared the results of stage IV colorectal cancer patients treated within a large Dutch phase III trial (CAIRO), in which standard chemotherapy and standard safety eligibility criteria were used, to patients treated outside the trial during the trial accrual period in a representative selection of 29 Dutch hospitals. Non-trial patients were identified by the Netherlands Cancer Registry (NCR), and were checked for the trial eligibility criteria. Results. The NCR registered 1946 stage IV colorectal cancer patients who received chemotherapy, of whom 394 patients were included in the CAIRO trial and 30 patients in other trials. Thus, the CAIRO trial participation rate was 20%. In the 29 hospitals, 162 patients received chemotherapy in the trial and 396 patients received chemotherapy outside the trial. Of the non-trial patients, 224 patients fulfilled the trial eligibility criteria. The overall survival of eligible non-trial patients was comparable to trial patients (HR 1.03, p = 0.70). However, non-eligible non-trial patients had a significantly worse outcome (HR 1.70, p < 0.01). Conclusion. These data provide evidence in a common tumor type that trial results have external validity, provided that standard eligibility criteria are being observed. Our finding of a worse outcome for patients not fulfilling these criteria strongly argues against the use of cancer treatments in other patient categories than included in the original trials in which these treatments were investigated.