We present a one-pot solution method to fabricate bicontinuous nanoporous organic framework membranes and their bio-catalytic applications. Temporary spinodal microstructures of phase-separating sol mixtures transform directly to covalent frameworks upon evaporation of solvent. The sol mixture consists of a linear polymer and a reactive network nanoparticle in an organic solvent, in which the nanoparticle is a cross-linked molecular level network and grown to a few tens of nanometers via solution-polymerization of di-isocyanate and tetra-amine monomers below the critical gelation point of concentration or temperature. Phase-separation-induced cross-over of sol-gel boundary is most likely a mechanism for capturing spinodal decomposition. Bicontinuous nanoporous membranes are obtained by extraction of the soluble polymer from the gelled network/polymer blend. The resultant nanoporous frameworks are built upon molecular networks, and thus exhibit superior chemical, thermal, and dimensional stabilities. A wide variety of new covalent framework materials can be derived by varying the chemical structures and compositions of the constituents. Their properties may be customized for different applications. We demonstrate that the bicontinuous nanoporous framework membrane can be utilized as an efficient nano-cage into which enzymes can be loaded quantitatively by simply applying pressurized solutions. The resultant enzyme-caged membranes show long-term stability and reusability in biocatalytic reactions operated in batch or continuous flow mode.