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Here we review the clinical trials that specifically enrolled patients with BRAF-mutated CRC, from the phase I/II studies to the phase III trial BEACON CRC. We also examine the future directions towards a molecularly guided therapy for patients with BRAF-mutated CRC and the crucial role of a molecularly and clinically based algorithm in order to offer the best choice of treatment for these patients.Virtual clinical trials (VCT) are in-silico reproductions of medical examinations, which adopt digital models of patients and simulated devi