Noble metal-free and highly efficient electro-catalytic materials with hierarchically porous structures continue to be studied for the oxygen reduction reaction (ORR) in microbial fuel cells (MFCs). We report bimetal-organic framework (bi-MOF)-derived nanocubic Swiss cheese-like carbons with a novel three-dimensional hierarchically porous structure (3D Co-N-C) prepared by utilizing cetyltrimethylammonium bromide (CTAB) as a structure-directing agent to control the formation of a nanocubic skeleton, and silica spheres as a template to form a mesoporous structure. The elemental composition and chemical morphology of this material can be tuned through the Zn/Co ratio to optimize its ORR catalytic activity. The optimized 3D Co-N-C displays excellent ORR catalytic performance (half-wave potential as high as 0.754 V vs. reversible hydrogen electrode and diffusion-limiting current density of 5.576 mA cm−2) in 0.01 mol L−1 phosphate-buffered saline (PBS electrolyte), showing it can compete with the commercial 20 wt% Pt/C catalysts. The catalytic capability and long-term durability of 3D Co-N-C as an air-filled cathode electrocatalyst in an MFC device are tested, showing that the 3D CoNC-MFC can reach a high power density of 1257 mW m−2 and provide a competitive voltage during a periodic feeding operation for 192 h; these values are much higher than those of the Pt/C-MFC.