Atomic-level control of the surface composition and atomic arrangement of multimetalic alloy nanocatalyst has emerged as an effective strategy to optimize their catalytic performance. By integrating the space-confined alloying and surface engineering strategies, we demonstrate a new class of core-shell structured PtFe@PtRuFe nanocatalyst, composed of an ordered PtFe intermetallic core with a 3-5 atomic-layers-thick PtRuFe shell. The well-defined PtFe@PtRuFe core-shell nanostructure exhibits excellent anti-CO poisoning ability and resistance to Fe leaching, achieving a factor of 1.68 enhancement in mass activity and a factor of 1.57 improvement in specific activity toward methanol oxidation reaction (MOR) compared to the state-of-the-art PtRu/C catalysts. Furthermore, the CO anodic oxidation on the PtFe@PtRuFe catalyst surface (0.39 V) starts much earlier than on the commercial PtRu/C (0.43 V) and Pt/C (0.83 V) catalysts. The enhanced MOR activity and anti-CO poisoning ability of the PtFe@PtRuFe catalyst is mainly attributed to the well-defined core-shell structure and favorable composition as well as the charge transfer from Fe/Ru to Pt and thusly be weakened Pt-COads adsorption energy. This novel core-shell structured nanocatalyst provide a new direction to reduce the usage of noble metal, tune the surface composition and atomic arrangement, enhance the activity and stability of multimetalic alloy nanocatalyst.