Chiral metal-organic frameworks with a three-dimensional network structure and wide-open pores (>30) were obtained by using chiral trifunctional linkers and multinuclear zinc clusters. The linkers, H₃ChirBTB-n, consist of a 4,4′,4′′-benzene-1,3,5-triyltribenzoate (BTB) backbone decorated with chiral oxazolidinone substituents. The size and polarity of these substituents determines the network topology formed under solvothermal synthesis conditions. The resulting chiral MOFs adsorb even large molecules from solution. Moreover, they are highly active Lewis acid catalysts in the Mukaiyama aldol reaction. Due to their chiral functionalization, they show significant levels of enantioselectivity, thereby proving the validity of the modular design concept employed.