You need time to fully understand the framework.
“For the average user, [..] the time required to understand the architecture of the framework far outweighs the menial task of coding it from scratch.” [Why I don’t use frameworks]
You need a close familiarity with your code’s architecture.
Using external CSS frameworks, you still need a profound understanding of your code. You need to know exactly how your framework is actually built. “By building a site from the ground up, you gain a knowledge of your site’s architecture that can’t be learned through any study or documentation.” [Why I don’t use frameworks]
You might inherit someone’s bugs or mistakes.
If you use external CSS Frameworks you might get in trouble fixing someone else’s bugs which is far more time-consuming than fixing your own bugs.
You develop sites upon a framework, not upon the solid knowledge of CSS.
“A big problem with frameworks is when up and coming developers attach themselves to a framework as opposed to the underlying code itself. The knowledge gained in this case surrounds a specific framework, which severely limits the developer.” [Please Do Not Use CSS Frameworks, by Jonathan Christopher]
You get a bloated source code.
“Whether it be in a server side language framework or JavaScript library, there is often a large percentage of code that will never be executed. While not a major issue server side, this can greatly degrade the performance of a client side framework such as a JavaScript library.” [Please Do Not Use CSS Frameworks, by Jonathan Christopher]
CSS can not be framed semantically.
“CSS and (X)HTML go hand in hand. (X)HTML is a language semantic in nature, which is impossible to wrap up in the style of a framework. Each and every project is unique in and of itself, right down to the document structure, classes, and ids. A CSS framework passively removes a great majority of semantic value from the markup of a document and, in my opinion, should be avoided.” [Please Do Not Use CSS Frameworks, by Jonathan Christopher]
Ignoring the uniqueness of your projects.
Designs should be based upon the content, not upon a standard template you use over and over again.