Mesoporous materials suffer from limitations including poor crystallinity and hydrolytic stability, lack of chemical diversity, insufficient pore accessibility, complex synthesis and toxicity issues. Here the association of non-toxic Zr-oxo clusters and feedstock isophthalic acid (IPA) via a Homometallic-Multicluster-Dot strategy results in a robust crystalline mesoporous MOF, denoted as MIP-206, that overcomes the aforementioned limitations. MIP-206, built up from an unprecedented combination of Zr6 and Zr12 oxo-cluster inorganic building units into a single structure, exhibits accessible meso-channels of ca. 2.6 nm and displays excellent chemical stability under different hydrolytic and harsh conditions. Owing to the abundant variety of functionalized IPA linkers, the chemical environment of MIP-206 can be easily tuned without hampering pore accessibility due to its large pore windows. As a result, MIP-206 loaded with palladium nanoparticles acts as an efficient and durable catalyst for the dehydrogenation of formic acid under mild conditions, outperforming benchmark mesoporous materials. This paves the way towards the utilization of MIP-206 as a robust mesoporous platform for a wide range of potential applications. 10.13140/RG.2.2.27305.21600