Innominato PF, Karaboué A, Focan C, et al. - Given that the triplet combination of irinotecan, oxaliplatin and fluorouracil represents an active frontline regimen in metastatic colorectal cancer, but there exists scarce data regarding its use as salvage therapy, therefore, researchers investigated its safety as well as efficacy profiles with its circadian‐based delivery (chronoILFO5) as either first‐ or second‐line therapy, within the time‐finding EORTC 05011 trial. They examined toxicity and anti‐tumour activity separately in first‐ and second‐line settings. Overall 149 and 44 patients received treatment in first‐ and second‐line settings, respectively. At least one episode of severe toxicity occurred in 36 (24.7%) and 10 (22.2%) patients in first‐ and second‐line, respectively. An objective response rate of 62.3% and a median progression‐free survival and overall survival of 8.7 months and 19.9 months were conferred by frontline chronoIFLO5; corresponding figures in the second‐line were 37.5%, 6.7 months and 16.3 months. Overall, findings of international and prospective analysis showed that chronoIFLO5 has favourable safety and efficacy profiles, both as frontline and as salvage therapy against metastatic colorectal cancer. Especially in second‐line, encouraging activity was evident, with limited haematological toxicity.