BGB-283 is a potent and selective RAF Kinase and EGFR inhibitor. BGB-283-displays potent antitumor activity in B-RAF mutated colorectal cancers. In vitro, BGB-283 potently inhibits B-RAFV600E-activated ERK phosphorylation and cell proliferation. It demonstrates selective cytotoxicity and preferentially inhibits proliferation of cancer cells harbouring B-RAFV600E and EGFR mutation/amplification. In B-RAFV600E CRC cell lines, BGB-283 effectively inhibits the reactivation of EGFR and EGFR-mediated cell proliferation. In vivo, BGB-283 treatment leads to dose-dependent tumor growth inhibition accompanied by partial and complete tumor regressions in both cell-line derived and primary human colorectal tumor xenografts bearing B-RAFV600E mutation. BGB-283 as a potent antitumor drug candidate with clinical potential for treating CRC harbouring B-RAFV600E mutation.