The first enantioselective formal [3 + 2] cycloaddition between α-isocyanoesters and trifluoromethylketones to give 5-trifluoromethyl-2-oxazolines bearing two contiguous stereogenic centers, one of them being a quaternary stereocenter substituted with a CF3 group, has been developed. The reaction is based upon a multicatalytic approach that combines a bifunctional Brønsted base-squaramide organocatalyst and Ag+ as Lewis acid. The reaction could be achieved with a range of aryl and heteroaryl trifluoromethyl ketones, and the resulting oxazolines were obtained with good to excellent diastereo- and enantioselectivity.